Download Helicobacter pylori bacteria: Tools for Eradication

Helicobacter pylori bacteria:
Tools for Eradication
By: Rachel Olivier, MS, ND, PhD
The mammalian intestinal tract contains a complex, dynamic,
and diverse society of nonpathologic bacteria. Undeniably,
the number of bacteria that colonize the human body is so
large that researchers have estimated that of the total number
of cells in the human body, estimated at 1014 (100 trillion)
cells, only 10% are not bacteria and belong to the human
body proper.1 Indeed the human large intestine is portrayed
as a complex microbial ecosystem.
Many of these bacteria serve beneficial purposes in the intestinal tract, such as assisting with digestion, and in the making
and processing of both short-chain fatty acids (SCFA)2, 3, 4 and
amino acids, in addition to their vital association with the intestinal epithelial cells, which affords immune homeostasis.5
Additionally, recent evidence has singled out the epithelial
cell-bacterial interaction, and its function in inhibiting the inflammatory signaling cascades via its action on blocking the
activation of NF-κB.5 In spite of these beneficial functions,
the intestinal tract may become populated with noncomensal flora, one of these species being Helicobacter pylori (H.
pylori) (formerly Campylobacter pylori), resulting in gastric
distress and suboptimal gastric function. Bacterial imbalance
in the colon has been described in IBD,6 as well as in association with the development of a colitogenic flora.5 Colonization of the gastric mucosa by non-commensal flora, including
H. pylori, has been associated with diminished gastric health
and associated illnesses.7 An added compounding factor associated with H. pylori infection is iron deficiency anemia,
established as an independent risk factor in both adolescent
children8 and adults.9
The bacterium H. pylori is characterized as a flagellated,
curved or S-shaped gram-negative rod10 that is able to penetrate the gastric mucosa and colonizes the gastric epithelium
of humans, resulting in persistent infection with possible
complications.11 The parietal cells of the stomach secrete profuse amounts of hydrochloric acid, which serves to maintain
the acidic environment stomach, characteristically at a pH
of less than two (<2).12 Despite this highly acidic environment, H. pylori is able to persist, thought to be due primarily
to its characteristic spiral morphology, and its high motility.13
Acute H. pylori induced gastritis is associated with hypochlorhydria,14 and colonization is speculated to have the ability
to modify the net gastric acidity, but virtue of the substances
the bacterium secretes.15,16 H. pylori infestation is associated
with a dysregulation in the function of the gastric epithelial
barrier,17 as well as with increased epithelial permeability.18
Once acquired, H. pylori can inhabit the human stomach for
years, decades, or possibly for life.
LIT-154
Rev. 7/09
By design the stomach is able to withstand a highly acidic
state. As noted above the optimum pH in the stomach is below 2.0. In addition to its digestive nature, this low pH serves
several other purposes, including the ability to destroy incoming bacteria, yeasts or parasites, the ability to release intrinsic
factor for the absorption of vitamin B12, the capability to absorb minerals, to trigger the release of enzymes and hormones
by the pancreas and intestines, and to trigger the enzyme pepsin, which is utilized in the breakdown of proteins into amino
acids. Besides these, a more debilitating consequence resulting from the lack of or suboptimal gastric pH is undigested
proteins, which make their way into the intestines. These
proteins in turn trigger an immune response, which results
in the production of inflammatory substrates. Consequently,
this may ultimately result in food allergies or more seriously
“leaky gut,”19 which is correlated to the consequent production of inflammatory cytokines and prostaglandins. Thus, the
root cause of infection with H. pylori may indeed be a deficiency in the production of hydrochloric acid.19
As a result of the common use of both acid suppressing
drugs and non-steroidal anti-inflammatory drugs (NSAID),
an escalating incidence in the colonization by H. pylori has
been observed. The allopathic medical community associates
the colonization of H. pylori with the development of peptic
ulcers, gastroduodenal inflammation, and gastric carcinoma,20, 21 in addition to disease conditions such as ankylosing
spondylitis,22 inflammatory bowel disease,23 and idiopathic
thrombocytopenic purpura.24 The risk for colonization is also
increased with immunosuppressant type therapies, including
the use of drugs such as corticosteroids or prednisone.25, 26
Oxidative stress is another factor implicated in the pathogenesis of H. pylori, said to result as a consequence of the associated cellular damage due to colonization of the bacterium.
This activity is postulated to result due to either an increase
or decrease in the expression of specific proteins, which are
associated with cell proliferation, carcinogenesis, cytoskeletal function and cellular defense mechanisms.27
In regards to NSAID use, H. pylori infection is indicated as
an independent risk factor for the development of peptic or
bleeding ulcers, with additive implications indicated when
these factors are correlated.28 Added to the use of acid suppressing drugs, H. pylori infection is associated with lower
acid secretion, attributed to the induction of an immune
response, resulting in the synthesis and production of interleukin 1 (IL-1), which is a potent inhibitor of gastric acid secretion.29 The overuse of acid suppressants, which in reality may
offer little to no benefit for the patient, further compounds this
scenario. In fact it has been documented that patients on proton pump inhibitors demonstrated benefits from the approved
indications of these drugs in only 37% of the cases.30
Published in The Original Internist June 2009 Vol. 16, No. 2
The fact that H. pylori can live and survive in the hostile acidic environment of the gastric mucosa is proposed to result
as a consequence of a pH gradient across its cell envelope.31
It also possesses the ability to produce unusually high levels
of urease, which is presumed to be critical for its colonization. High levels of urease result by virtue of its capability to
hydrolyze urea, resulting in the production of ammonia. As
a consequence of its ammonia producing ability, a thin acidneutralizing layer, or “cloud” is formed around the bacterium,
which in turn protects it from destruction by the acidic environment of the gut.32 The production of urease, therefore, has
been associated with a protective effect on the bacterium.33
There has been a growing interest in a phytochemical
approach to the eradication this bacterium, primarily due
to the decline in efficacy of the currently used drugs for
treatment. Specific botanical preparations have documented
benefits in supporting gastrointestinal health, as well as in
mitigating H. pylori.
Phytochemical Support for Bacterial Eradication
Berberine. Berberine is isolated as the main alkaloid derived from the roots and bark of Berberis vulgaris, a deciduous shrub, native to Central and Southern Europe, Northwest
Africa and Western Asia. Significant antimicrobial activity
against a variety of organisms, including bacteria, viruses,
fungi, parasites (including Giardia lamblia, and Entamoeba
histolytica) protozoans, (including Trichomonas vaginalis34)
helminths, and chlamydia has been documented with Berberine extracts and decoctions.35, 36
The inhibitory effect of berberine on the growth of H. pylori
is well recognized,37 and its antiproliferative action, in a dosedependent manner, has been confirmed. The later attribute
has been correlated to its action via the mitochondrial/caspase-dependent pathway.38 In vitro studies have demonstrated
berberine’s ability to interact with nucleic acids, in particular
DNA.39 Berberine has also been demonstrated to induce G0/
G1 cell cycle arrest in an animal model,40 to selectively inhibit
the cell cycle at G2/M in a cell line model (Balb/c 3T3),41, 42
and to decrease experimentally induced apoptosis in a concentration- and time-dependent manner.43, 44
Wild Indigo (Baptisia tinctoria). Baptisia tinctoria, commonly known as Wild Indigo, is an herbaceous perennial
herb. The herb is noted for both its astringent45 and immune
stimulating properties.46,47 Traditionally used by North Americans Indians for its antiseptic properties, it is also a noted
antibacterial cleansing agent.48,49 It has been associated with
the promotion of normal cellular metabolism and in the support of healthy tissues.50
The chemical constituents of the root consists of glycoproteins, quinolizidine alkaloids, including cytisine and
anagyrine, isoflavanoids, hydroxycumarins, and polysaccharides, including arabinogalactans.51 Use has been associated
with supporting the body’s natural resistance to microorganisms and toxins via its activation of macrophages, and due to
an increased production of interleukin-1. In animal studies
the polysaccharide and glycoprotein fraction was demonstrated to produce an immune-stimulating effect.51 Other research
supports the use of arabinogalactan components for their antiinflammatory and immunostimulating properties.52
Licorice (Glycyrrhiza glabra). Licorice is a perennial herb or
sub-shrub containing numerous active compounds, including
flavonoids, triterpene saponins, isoflavonoids and hydroxycoumarins. Of these, the component possessing the greatest
activity is the triterpenoid saponin glycyrrhizin (GL), having
demonstrated antiviral53, 54, 55, 56 antimicrobial57 and antifungal58,59 properties.
In animal studies GL was demonstrated to stimulate interferon gamma production by T-cells,60 resulting in an antiviral
effect,61 and to augment the activity of natural killer cells.62 In
the human intestinal tract GL is converted primarily to its biologically active metabolite glycyrrhetinic acid (GA), and to
a lesser extent to glycyrrhetinic acid-3-O-beta-D-glucuronide
(GAMG) by the intestinal microflora.63,64 Both GL and GA
have demonstrated anti-inflammatory properties.63,65 GL
has also been demonstrated to impair the growth of H. pylori in vivo, via the inhibition of the activity of arylamine Nacetyltransferase (NAT family of enzymes).66 This family of
enzymes functions to catalyze the transfer of acetyl groups
from acetyl-coenzyme A to an aromatic amine, heterocyclic
amine or hydrazine compound.67 In a separate in vitro study
GA, at a concentration of ≤50mg/L, was demonstrated to
inhibit 79% (23/29) of the H. pylori stains tested, including
two clarithromycin-resistant strains, noting both concentration- and strain-dependent bactericidal effects of GA.65 A
more recent in vitro study utilizing PC12 cells demonstrated
that treatment with GA resulted in a neuroprotective effect, by
virtue of a decrease in ROS, via the elevation of glutathione
peroxidase and catalase, with a corresponding decrease in mitochondrial membrane potential. The authors concluded that
GA treatment may play a role in modulating both the intracellular antioxidant system and mitochondria-induced apoptosis,
resulting in cellular protection from ischemic injury.68
Clove (Syzygium aromaticum). Clove is a plant indigenous to
the Moluccan Islands of Indonesia. It is cultivated on these
islands, as well as in other tropical regions, including Tanzania, Madagascar and Brazil. Its active compounds include
its volatile oils, flavonoids, tannins, triterpines and steroids,
including beta-sitosterol.69 The main component eugenol,
comprising 85-95%, has been associated with the prevention
of lipid peroxidation70 and is recognized as a strong scavenger
of active oxygen radicals.71 It is considered an effective antimicrobial agent and has use as an antiseptic.72
A number of studies have demonstrated clove’s activity
against various bacterial species,73 including Bacillus subtilis,74 Campylobacter jejuni, Salmonella enterides, Staphylococcus aureus and E. coli.75 An aqueous infusion of cloves
was demonstrated to restrict cellular invasion, resulting in a
notable reduction in the incidence of skin papilloma in animals, as well as in the multiplicity of the growth, in a dose
dependent manner. At the most effective oral dose (100 μl/
day), no adverse or toxic effects were noted.76 It has also been
specifically demonstrated to inhibit the growth of H. pylori.77
Clove is approved by the German Commission E for use as a
topical antiseptic and as an anesthetic for inflammation.78
Slippery Elm (Ulmus fulva). Slippery Elm has been used for
centuries by North American Indians for skin irritations including, wounds, boils, ulcers, burns, and skin inflammation,
as well as orally for the relieve of coughs, sore throats, diarrhea, and stomach problems.79 The powdered inner bark has
mucilaginous qualities, which is indicated for relief of irritation of the mucus membranes, and may be useful for treating
irritation or ulceration of the stomach lining and duodenum.80
Its mucilaginous characteristics also contribute to its noted
action, that of acting as a coating. In this regard it acts to
soothe the mouth, throat, stomach, and intestines.79
Barberry (Berberis vulgaris). B. vulgaris is native to most of
Europe. Its root bark contains several isoquinoline alkaloids
including berberine, berbamine, and oxyacanthin. The root
bark is also a source of vitamin C (citric acid), and contains
chelidonic, malic and tartaric acids.81 It possesses mild diuretic qualities,82 and also has confirmed anti-inflammatory
properties.83 Furthermore, studies have validated the antiinflammatory action of berberine, demonstrating a significant
down-regulation in the expression of pro-inflammatory genes
including TNF, IL-1, IL-6, MCP-1, iNOS and COX2 with
treatment.84, 85
Berberine, a major alkaloid of Barberry possesses anti-inflammatory properties, having demonstrated to effectively
inhibit, in a dose- and time-dependent manner, COX-2 transcriptional activity in a malignancy cell model,86 as well as to
reduce prostaglandin E2 (PGE2) production. The latter effect was noted to also result in a reduction of COX-2 protein
production.87 In a separate study berberine was demonstrated
to decrease both the expression and protein binding on the
hypoxia-response element of the vascular endothelial growth
factor (VEGF). VEGF is a critical growth factor in tumor
angiogenesis.88 Based on in vitro studies, it was proposed that
berberine’s action in vivo may be ‘in abolishing the angiogenic function of vascular endothelial cells, preventing them
from responding to the call for angiogenesis, and may also
prevent hypoxic tumor cells from inducing angiogenesis,’
thus retarding cellular proliferation. In fact hypoxia induced
VEGF expression was demonstrated to be completely inhibited by berberine.89
Myrrh (Commiphora molmol). C. molmol is a highly valued
botanical medicine in Ayurveda, the Indian system of medicine, as represented by the wide variety of Ayurvedic formulas containing Myrrh. In Arab medicine, C. molmol is used as
part of a polyherbal formulation to improve digestion and to
treat gastrointestinal maladies.90, 91, 92 Its action is attributed to
its positive effect on inflammation.93
In studies utilizing myrrh, a wide range of inhibitory action against both Gram (+) and Gram (-) bacteria has been
demonstrated.94 Myrrh, in a dose-dependent manner, was
also demonstrated to protect the gastric mucosa against the
necrotizing effects of various agents. This protective action
was attributed to its positive effect on mucus production, as
well as to its ability to increase both nucleic acid production,
and the concentration of non-protien sulfhydryl compounds,
noted for both their involvement in maintaining gastroduodenal integrity, as well as in the protection they offer against
chemically-induced lesions in cells, tissues and organs.95, 96, 97
These actions were associated to Myrrh’s ability to scavenge
free radicals, as well to its thyroid-stimulating and prostaglandin-inducing properties.98 Endogenously produced prostaglandins have been attributed to functioning as activators
of potassium ATP channels, which has been demonstrated in
part to mediate gastroprotection.99
Oregon Grape (Berberis aquifolium). The major components of Berberis are berberine, a yellow colored isoquineoline alkaloid, beramine and oxyacanthine, which are both
white alkaloids, along with phytosterin, gum and sugar. As
noted above the medicinal value of Berberis is thought to be
due to its high content of isoquineoline alkaloids, especially
berberine, which is postulated to have antibiotic activity.100
Its actions are noted in promoting excretion and secretion,
improving digestion and assimilation, and in stimulating the
lymphatic system. It is documented as having an ‘invigorating power over the gastric functions.’101
Select Minerals as Beneficial Adjuncts for Bacterial
Eradication.
Bismuth citrate. Bismuth is a naturally occurring mineral
that has documented activity against H. pylori.102, 103 Bismuth
salts have been used extensively for the alleviation of gastrointestinal irritation, as well as for irritation of the stomach
and bowels.104 Standard preparations of bismuth are used to
decrease the flow of fluids and electrolytes into the bowel, to
reduce inflammation within the intestine, and may serve to
alleviate the diarrhea causing organism.105 Preparations are
recognized as safe when taken as directed.106
Bentonite clay. Bentonite is an absorptive and colloidal clay,
demonstrated to be a very effective absorber of toxins.107 In
one study a hepato-nephro (liver-kidney) protective effect
against aflatoxins was demonstrated with bentonite use, indicating that it ‘diminished most of the deleterious effects of the
aflatoxin.’ This effect was attributed the suppressive effect
it exerted against chromosomal aberrations.108
The inflammatory response to H. pylori is well documented,
implicated to result in cellular proliferation and gastric mucosal damage. H. pylori components have been demonstrated
to act directly on gastric epithelium and to induce an increased
release of cytokines.109 These actions have been primarily
attributed to the up-regulation of inflammatory markers,
including COX-2 and IL-1β.110 To curtail this deleterious effect on the gastric mucosa, a comprehensive blend of phytochemical nutrients, known to have a positive impact on the
gastrointestinal tissues, may aide in healing and repairing these
tissues. The eradication of H. pylori is indeed beneficial, specifically when coupled with gastric complications, as recently
demonstrated in a Japanese trial involving 544 patients with
early gastric cancer. In this study the eradication of H. pylori was associated with a greatly reduced risk for recurring
gastric cancer.111 Select herbs and minerals are recognized
as possessing anti-pylori activity, noted to downregulate
inflammatory markers associated with H. pylori infestation
and correlated to gastric inflammation. Added to this, the use
of specific herbal components has demonstrated a positive
effect in reducing the antigens associated with H. pylori.
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